Compositions and methods for treatment and imaging using nanoparticles
The present invention encompasses compositions comprising two spectrally distinct radionuclides separated by a site susceptible to cleavage. Compositions of the invention may be used to detect enzyme activity and/or image diseases associated with said enzyme activity.
1. A composition comprising:
(a) a peptide comprising the hydrophobic amino acid sequence SEQ ID No. 4 (Tyr-Leu-Ala-Ile-Ahx-Pro-Ala) and the hydrophilic amino acid sequence SEQ ID No. 3 (Gly-Arg-Arg-Arg-Orn-Arg-Arg-Lys-Lys-Arg-Lys) separated by the caspase-3 sensitive site comprising the amino acid sequence SEQ ID NO:2 (Asp-Glu-Val-Asp); and
(b) two radionuclides, wherein the spectrally differentiated radionuclides are 125 I and 111 In
wherein the radionuclides are attached to the peptide and separated by the site susceptible to cleavage by caspase-3.
2. The composition of claim 1 , wherein one of the radionuclides is conjugated to a Tyr residue found in the peptide.
3. The composition of claim 1 , wherein one of the radionuclides is conjugated to a chelating agent coupled to the peptide.
4. The composition of claim 3 , wherein the radionuclide is 111 In.
5. The composition of claim 1 , wherein the peptide further comprises a -Lys-Gly-Cys- group and one of the radionuclides is conjugated to the -Lys-Gly-Cys- group found the peptide.
6. A method of detecting enzyme activity in a subject, the method comprising:
a) administering to the subject an effective amount of a composition of claim 1 ;
b) imaging the subject for a signal corresponding to the 125 I and 111 In to determine the biodistribution for the 125 I and 111 In; and
c) comparing the biodistribution of the 125 I to the biodistribution of the 111 In wherein when the biodistribution for the 125 I differs from the biodistribution for the 111 In, enzyme activity is detected.
7. The method of claim 6 , wherein the subject is imaged about 4 to about 48 hours after administration.
8. The method of claim 6 , wherein the subject is imaged using single photon emission computed tomography (SPECT).